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A SUITABLE BIOASSAY IS NEEDED TO MODEL LATHYRISM IN MONO-GASTRIC ANIMALS Dirk Enneking School of Food and Agriculture, University of Adelaide, Waite Agricultural Research Institute, Waite Rd. Glen Osmond , 5064 South Australia (Australia).

Neurolathyrism is intricately linked to famine (due to drought or conflict), poverty and malnutrition .

Ortiz de Landazuri (1944) “ in the presence of a protein poor diet (2000 kilo calories/day), 70 g/day of Lathyrus sativus do not produce lathyrism. Up to 300 g of L. sativus can be consumed/day in the presence of protecting factors derived from better quality food (meat, cheese, milk) without provoking lathyrism. A higher dose of L. sativus leads to lathyrism even in the presence of protecting factors.”

Which nutrients are in short supply when a monotonous diets of grasspea or incompletely processed cassava is consumed for extended periods of time ? Which animal bioassay allows us to model neurolathyrism and Konzo?

Lathyrism in animals Neurolathyrism in animals Lathyrism in the horse hindleg paralysis and and hoaring. Death occurs due to asphyxiation. Large animals such as the horse are more frequently affected than small animals (Maleval, 1927)

Neurolathyrism in animals. Numerous studies feeding grasspea to a variety of animals have produced mixed results (Fumarola and Zanelli, 1914)*. Geiger et al. (1933) suggested that the differences in susceptibility of individual animals is related to the quality of the base diet used in these experiments. =>a poor quality base diet is likely to succeed better than an optimally balanced one to produce neurodegenerative symptoms *Fumarola, G. and Zanelli, C. F. (1914). Anatomische experimentelle Forschungen ueber den Lathyrismus. Archiv Fuer Psychiatrie Und Nervenkrankheiten 54 (2)489-536

B group vitamins are all co-enzymes. They comprise: B1 thiamine, aneurine B2 riboflavin B3 niacin, nicotinic acid B6 pyridoxine B12 cobalmin, cyanocobalmin Biotin, folic acid, pantothenic acid B group vitamins and vitamin C are water soluble and not stored in sufficient quantities in organisms Insufficiences Vitamins A,D,E, and K are all fat soluble and stored easily Less likelyhood of insufficiencies.

B group vitamins are all co-enzymes. They comprise:

B1 thiamine, aneurine

B2 riboflavin

B3 niacin, nicotinic acid

B6 pyridoxine

B12 cobalmin, cyanocobalmin

Biotin, folic acid, pantothenic acid

B group vitamins and vitamin C are water soluble and not stored in sufficient quantities in organisms

B12 Important for all cells, particularly the nervous system. Deficiencies lead to subacute degeneration of the spinal chord. It is not found in significant amounts in plant foods but can be sourced from animal products (eggs, dairy, meat, liver, kidney, heart) The B complex in general is involved in red blood cell formation , the normal functioning of the gastrointestinal tract and the metabolism of protein . Sources: dark-green vegetables, legumes , whole grain, yeast, heart and pancreas.

The results of laboratory diet were normal b) Anatomical hurts were more important and extensive proceeding from exclusive diet flour and total and partial adjusted diets c) They were extensive and steady subarachnoid, pial and subpial hemorrhages (excepting in those with salt depletion); demyelinisation, specially at the Corpus callosum and the white matter of the small cerebellar lobes; both Bergmann's and Alzheimer's ameboid types of gliosis d) Neuronal changes overweighed in Ammon's horn area (Fascia dentata and Stratum pyramidale) e) The hemorrhagic condition as a whole was similar to that of human internal hemorrhagic pachymeningitis f) Morphological changes had no resemblance with those of deficiency diseases , because they were limited to a Nissl's chronic disturbance pattern g) Exclusive daily food of blue vetch peas flour (Lathyrus sativus) as well as added with another complementary food (mixed diet) results in an endemic lathyritic condition. It is in strong nutritional indigence of exceptional times that such exclusive diet of flour originates the classic epidemical lathyrism h) At present, both the clinical observations and the biochemical findings (Adiga's, Murti's, Rao's and Bell's tests) as well as our histopathological data, all support the toxic etiology of human lathyritic disease.

The results of laboratory diet were normal

b) Anatomical hurts were more important and extensive proceeding from exclusive diet flour and total and partial adjusted diets

c) They were extensive and steady subarachnoid, pial and subpial hemorrhages (excepting in those with salt depletion); demyelinisation, specially at the Corpus callosum and the white matter of the small cerebellar lobes; both Bergmann's and Alzheimer's ameboid types of gliosis

e) The hemorrhagic condition as a whole was similar to that of human internal hemorrhagic pachymeningitis

f) Morphological changes had no resemblance with those of deficiency diseases , because they were limited to a Nissl's chronic disturbance pattern

g) Exclusive daily food of blue vetch peas flour (Lathyrus sativus) as well as added with another complementary food (mixed diet) results in an endemic lathyritic condition. It is in strong nutritional indigence of exceptional times that such exclusive diet of flour originates the classic epidemical lathyrism

h) At present, both the clinical observations and the biochemical findings (Adiga's, Murti's, Rao's and Bell's tests) as well as our histopathological data, all support the toxic etiology of human lathyritic disease.

Conclusion Neurolathyrism and Konzo are intricately linked to nutritional deficiencies. To model these and other nutritional neuropathies, a malnutrition animal model is needed. Legumes deplete sulfur amino acids (saa) in their predators, suggesting that adequate saa supplementation protects against neurolathyrism. Additional neuroprotective nutrients ie. olive oil may also play a role. Genetic animal models may help to dissect the underlying mechanisms.

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